Fangchinoline exerts anticancer effects on colorectal cancer by inducing autophagy via regulation AMPK/mTOR/ULK1 pathway.

Autophagy has become a promising target for cancer therapy. Fangchinoline (Fan) has been shown to exert anticancer effects in some types of cancers. However, the anticancer effects on colorectal cancer (CRC) and the underlying mechanisms have never been elucidated. More specifically, regulation of autophagy in CRC by Fan has never been reported before. In the present study, Fan was found to induce apoptosis and autophagic flux in the CRC cell lines HT29 and HCT116, which was reflected by the enhanced levels of LC3-II protein and p62 degradation, and the increased formation of autophagosomes and puncta formation by LC3-II. Meanwhile, combination with the early-stage autophagy inhibitor 3-methyladenine (3-MA) but not the late-stage autophagy inhibitor chloroquine (CQ) further increased Fan-induced cell death, which suggested the cytoprotective function of autophagy induced by Fan in both HT29 and HCT116 cells. Moreover, Fan treatment demonstrated a dose- and time-dependently increase in the phosphorylation of AMPK and decrease in the phosphorylation of mammalian target of rapamycin (mTOR) and ULK1, leading to the activation of the AMPK/mTOR/ULK1 signaling pathway. Furthermore, in the HT29 xenograft model, Fan inhibited tumor growth in vivo. These results indicate that Fan inhibited CRC cell growth both in vitro and in vivo and revealed a new molecular mechanism involved in the anticancer effect of Fan on CRC, suggesting that Fan is a potent autophagy inducer and might be a promising anticancer agent.

Prevalence of microplastics in animal-based traditional medicinal materials: Widespread pollution in terrestrial environments.

Microplastics (MPs) pollution is an emerging environmental and health concern. MPs have been extensively observed in the aquatic environment, yet rarely investigated in the terrestrial ecosystem, especially in relation to health risks. To evaluate potential MPs pollution in land-dwelling animal medicine materials, we collected 20 types of small animal-based medicinal materials and 10 types of available fresh terrestrial animals from eight different regions in China. MPs were found in all medicinal materials with an average incidence rate of 94.67%. The abundance of MPs was in the range of 1.80 ± 0.38 to 7.80 ± 0.83 items/individual or 1.59 ± 0.33 to 43.56 ± 9.22 items/g (dry weight), with polymer distribution by polyethylene terephthalate (40.45%), rayon (30.64%), polyethylene (10.11%), nylon (7.35%), polypropylene (5.93%), and polyvinyl chloride (5.52%). The majority of MPs were microfibers (84.68%), with 15.32% of fragments. Moreover, MPs were directly observed in the intestine, detected in all ten types of fresh medicinal animals with the abundance of 0.83 ± 0.35 to 3.42 ± 0.46 items/individual. Furthermore, significant positive correlations (R: 0.32-0.99, p < 0.05) of MPs characteristics were found between medicinal materials and fresh animals, including shape, size, color, and polymer distribution of MPs. The results support that MPs in the medicinal materials were likely derived from living animals. This study demonstrates the prevalence of MPs in animal-based, traditional medicinal materials, and also suggests widespread MPs pollution in terrestrial environments and latent health risks.

Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults.

PURPOSE: To establish a correlation between putative iron content using susceptibility weighted imaging (SWI) phase and T2* weighted magnitude values in the basal ganglia and the thalamus as a function of age in healthy human brains. MATERIALS AND METHODS: One hundred healthy adults (range, 20-69 years; mean, 43 years) were evaluated for this study using a gradient echo sequence. The original magnitude and high pass filtered phase data were analyzed as proxy variables for iron content in the substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus, and pulvinar thalamus. Each structure was broken into two parts, a high iron content region and a low iron content region. RESULTS: Both magnitude and phase data showed an increase in putative iron content with age. However, the high iron content region revealed two new pieces of information: both the average iron content per pixel and the area of high iron increased with age. Furthermore, significant increase in iron uptake as a function of age was found past the age of 40. CONCLUSION: A two region of interest analysis of iron is a much more sensitive means to evaluate iron content change over time. Contrary to the current belief that iron content increases level off with age, the putative iron deposition in the high iron content region is seen to increase with age.

Magnetic resonance spectroscopic imaging detects abnormalities in normal-appearing frontal lobe of patients with Sturge-Weber syndrome.

BACKGROUND: In Sturge-Weber syndrome (SWS), structural MRI abnormalities are most common in the posterior brain regions. Frontal lobe involvement increases the risk of motor impairment. The goal of this study was to determine whether Magnetic Resonance Spectroscopic Imaging (MRSI) can improve detection of frontal lobe involvement in children with SWS. METHODS: Sixteen children (age: .9-10.4 years) with unilateral SWS underwent MRI with MRSI prospectively. N-acetyl-aspartate (NAA) and choline asymmetries in the posterior and frontal regions were measured. RESULTS: Eight children presented normal-appearing frontal lobes on conventional MRI, but 7 of them showed abnormal NAA and/or choline content in the frontal lobe of the affected hemisphere. Lower frontal lobe gray matter NAA was associated with earlier onset of seizures (r= .76; P= .04) and impaired motor function (r=-.89, P < .001). Frontal NAA asymmetry was an independent predictor of motor function in a regression analysis (P= .01) CONCLUSION: MRSI is more sensitive than conventional structural MRI for detection of frontal lobe involvement in SWS. Decreased frontal lobe NAA is an excellent predictor of motor functions. Thus, MRSI can provide complementary information for the assessment of normal-appearing brain regions, and may assist prognosis evaluation in children with SWS.

MR imaging of the stomach: potential use for mangafodipir trisodium--a study in swine.

PURPOSE: To evaluate mangafodipir trisodium as a potential contrast agent at magnetic resonance (MR) imaging of the stomach. MATERIALS AND METHODS: Mangafodipir trisodium was injected intravenously into three swine at a dose of 5 micromol per kilogram of body weight. For comparison, gadopentetate dimeglumine was injected into three other swine at a dose of 0.1 mmol per kilogram of body weight. T1-weighted three-dimensional MR images were acquired in all six swine at 1.5 T before and approximately 10, 15, 20, 25, 30, and 40 minutes after contrast material administration. Extracted stomach specimens were imaged at 3.0 T. In vivo and ex vivo images were evaluated visually and quantitatively for contrast enhancement of the stomach, and in vivo images were evaluated for the presence of reflux from the duodenum. RESULTS: Mangafodipir trisodium produced prolonged and selective enhancement of the inner surface of the stomach, in contrast to the more general enhancement seen with gadopentetate dimeglumine, and reflux from the duodenum could not account for this selective enhancement. Ex vivo images confirmed that T1 enhancement in the stomach wall with mangafodipir trisodium was limited to the inner surface. Gadopentetate dimeglumine did not produce selective enhancement of the inner surface of the stomach. CONCLUSION: Mangafodipir trisodium preferentially enhances the inner surface of the stomach on MR images acquired in swine and, therefore, may have potential for use as a contrast agent at MR imaging of the human stomach.